A Study on the Effects of Combined FMT on Gut Microbiota and Eating Disorder Symptoms in an

Not Applicable

Not yet recruiting

• Conditions: Anorexia Nervosa
• Interventions: Drug: Placebo; Biological: Fecal Microbiota Transplantation

• Registration Number: NCT06744751
• Lead Sponsor: Shanghai Mental Health Center

Brief Summary

The goal of this clinical trial is to determine if Fecal Microbiota Transplantation (FMT) is effective in treating Anorexia Nervosa (AN). The study will also explore how FMT works. The main questions it aims to answer are:

1. What is the efficacy of combined FMT treatment in patients with AN?

2. What is the relationship between treatment efficacy and changes in gut microbiota, and what mechanisms underlie the effects of FMT in treating AN? Researchers will compare FMT to a placebo (a look-alike substance that contains no active ingredients) to see if FMT is effective in treating AN.

Participants will:

* Be hospitalized

* Take FMT or placebo daily for 12 days

* Provide stool and blood samples before and after FMT

* Visit the clinic every 4 weeks for check-ups and tests

Detailed Description

Anorexia Nervosa (AN) is a chronic, challenging psychiatric disorder characterized by an intense fear of gaining weight, extreme weight loss, severe malnutrition, and physical wasting. The core behavioral trait of AN is a "persistent restriction of energy intake," which results in low body weight, malnutrition, and, in severe cases, death due to multiple organ failure. Consequently, AN is considered the most fatal mental disorder. With globalization and rapid economic development in China, dieting and weight loss have become fashionable. A domestic survey found that 49.9% to 55.7% of female college students engage in dieting and weight loss behaviors, and the prevalence of AN in China has been increasing rapidly. Thus, AN is becoming a significant public health issue in China.

More than 90% of AN patients experience functional gastrointestinal symptoms (FGS), including bloating, constipation, and difficulty swallowing. These FGS are largely associated with disordered eating behaviors. For example, patients with restrictive eating often prefer high-fiber, low-fat, and low-carbohydrate foods, which can lead to symptoms such as early satiety, constipation, and flatulence. Therefore, disordered eating behavior can contribute to abnormal gastrointestinal function, while, conversely, disordered GI function can exacerbate the severity of AN, hinder patients from resuming normal eating habits, and impact the effectiveness of clinical treatment. Recent studies increasingly suggest that gut microbes play an essential role in influencing GI symptoms in psychiatric disorders.

The human gastrointestinal tract hosts billions of microorganisms, with a total gene count about 150 times greater than that of the human genome. These microorganisms are closely linked to the regulation of gastrointestinal function and have also been shown to influence mood, eating behavior, appetite, and nutrient metabolism. Researchers have discovered that Nod2 receptors expressed by inhibitory neurons in the hypothalamus and arcuate nucleus can directly sense cytosolic peptides produced by bacteria, regulating feeding behavior and suggesting that gut microbes may influence appetite through the brain-gut axis. Cross-sectional studies have found abnormalities in gut flora composition or metabolites in AN patients, while longitudinal studies have shown that the abundance of gut flora increases after weight regain in AN patients; however, flora diversity and gastrointestinal symptoms do not fully return to normal. This suggests that, while body weight may normalize, the gut microbiome remains "unhealthy."

Fecal Microbiota Transplantation (FMT) involves transplanting healthy intestinal flora into a patient's gut. FMT primarily treats digestive diseases like intestinal infections, irritable bowel syndrome, Crohn's disease, and chronic diarrhea, effectively relieving symptoms such as constipation and diarrhea. FMT has also been used to treat neuropsychiatric disorders like autism, mood disorders, ADHD, and sleep disorders. Studies have shown that FMT can alleviate symptoms of depression, anxiety, and sleep disturbances caused by chronic stress, reduce inflammatory responses to slow the progression of Alzheimer's disease, and improve symptoms in patients with autism spectrum disorder (ASD). Although some case reports describe FMT's application in AN patients, there is still a lack of extensive randomized controlled trials to validate its efficacy.

Currently, no studies have explored the role of FMT combined with conventional treatments in improving AN's clinical symptoms. Given that mood and GI symptoms are common comorbidities of AN, and there is no effective pharmacologic treatment for these symptoms, FMT offers a promising new strategy to enhance clinical outcomes as a supportive treatment for AN.

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-11-07
• Study First Submitted QC: 2024-12-17
• Last Update Submitted: 2024-12-17
• Study First Posted: 2024-12-20
• Last Update Posted: 2024-12-20
• Study Start: 2025-01-01
• Primary Completion: 2025-06-30
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

• Female, aged 12-35 years, meets DSM-5 diagnostic criteria for anorexia nervosa.
• BMI > 14 kg/m²; for children/adolescents, BMI > the 0.3 percentile for their age.
• Presence of digestive symptoms (e.g., constipation, bloating, diarrhea).
• Duration of the disease (since the onset of dieting and weight loss) is greater than three years.
• Has at least one of the following drug-resistant or treatment-resistant characteristics:
• Greater than or equal to two standardized inpatient treatments (in eating disorder diagnosis and treatment centers, both in Japan and abroad).
• Systematic psychotherapy (e.g., 10 or more sessions of ongoing psychotherapy) or 1 year of poor treatment despite full-dose and full-course antidepressants and/or atypical antipsychotics.
• Each patient must understand the nature of this study and sign an informed consent form.

Exclusion Criteria

• Co-morbid severe mental disorders such as schizophrenia, bipolar disorder, intellectual disability, persistent delusional disorder, schizoaffective disorder, or organic mental disorders.
• Substance abusers/addicts, individuals with a high suicide risk, or those with strong destructive impulses or antisocial behavior.
• Those with severe low body mass anorexia nervosa (e.g., blood pressure < 80/50 mmHg, heart rate < 40 beats/min, weight loss > 1 kg per week, or those requiring assistance in sitting or squatting in a prone position).
• Patients with severe somatic diseases or comorbidities, including:
• Organic intestinal lesions such as congenital megacolon, intestinal obstruction, or intussusception.
• Previous pathological intestinal inflammatory conditions such as inflammatory bowel disease.
• History of traumatic brain injury, cerebral palsy, encephalitis, or other organic brain disorders.
• Severe hepatic or renal insufficiency (defined as levels greater than three times the upper limit of normal).
• Pregnant or breastfeeding women.
• Use of medications such as probiotics or antibiotics that clearly affect the intestinal flora within 3 months prior to the visit or during the treatment.
• Any other reason that the investigator deems unsuitable for participation in this clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The placebo capsules, manufactured by the same company, are identical in appearance, size, color, dosage form, weight, and taste to the FMT capsules. Starch is used as the main ingredient to mimic the FMT capsules.
Fecal Microbiota Transplantation	Fecal Microbiota Transplantation	The FMT capsules used in this study contain processed, frozen stool from healthy donors, providing gut microbiota from these individuals. They are available in two doses: size 0 capsules contain 175 mg of bacterial powder, and size 3 capsules contain 85 mg of bacterial powder. The FMT capsules meet relevant manufacturing standards. Patients take the capsules once daily, with a dose of 4 capsules per day, over a period of 12 days (for a total of 48 capsules). Capsules are selected based on age: patients under 16 use size 3 capsules, while those aged 16 and older use size 0 capsules.

Primary Outcome Measures

Name	Time	Method
Hight	week 0(recruitment），week 2（baseline），week 4（post-intervention），week 8、12、16、20、24、28、32（follow-up）	Measurement of morning height will be taken using the same height-measuring device.
Weight	week 0(recruitment），week 2（baseline），week 4（post-intervention），week 8、12、16、20、24、28、32（follow-up）	Morning fasting weight will be measured using the same scale.

Secondary Outcome Measures

Name	Time	Method
Short-chain fatty acids	week 2（baseline），week 8（post-intervention），week 12（follow-up）	Blood was collected and centrifuged to obtain serum, which was then tested for short-chain fatty acids.
Eating Disorder Examination Questionnaire 6.0(EDEQ-6.0)	week 0（recruitment）， week 2（baseline）， week 4 （post-intervention），week 8、12、16、20、24、28、32（follow-up）	The Eating Disorder Examination Questionnaire 6.0 (EDE-Q 6.0) is a self-assessment questionnaire based on the Eating Disorder Examination (EDE). It evaluates the primary behavioral and psychological characteristics of eating disorders, measuring both the frequency and intensity of symptoms to assess disorder severity. The questionnaire includes four subscales: dietary restriction, eating concerns, body image concerns, and weight concerns.
Eating Disorders Inventory(EDI)	week 0（recruitment）， week 2（baseline），week 4（post-intervention），week 8、12、16、20、24、28、32（follow-up）	The Eating Disorders Inventory (EDI) consists of 64 items, divided into 8 factors: thinness tendency, body dissatisfaction, gluttony, perfectionism, interpersonal mistrust, fear of maturity, internal sense of feeling, and ineffectiveness. It is scored on a 6-point scale ranging from 1 (never) to 6 (always). The total score is the sum of the individual item scores, with a minimum score of 64 and a maximum score of 384. Higher scores indicate a greater likelihood of having an eating disorder.
Gastrointestinal Symptom Rating Scale(GSRS)	Week 0（recuitment）， week 2（baseline），week 4（post-intervention），week 8、12、16、20、24、28、32（follow-up）	The Gastrointestinal Symptom Rating Scale (GSRS) consists of 15 items designed to assess a patient's gastrointestinal symptoms over the past week. Each question is scored based on the degree, frequency, duration, mitigating factors, and impact on social activities, using a scale from 0 to 3, where 0 indicates no symptoms and 3 indicates very severe symptoms. The scores for each question are summed to give a total score, with a minimum of 0 and a maximum of 45. Higher scores indicate more severe gastrointestinal symptoms.
Beck Anxiety Inventory(BAI)	Week 0（recuitment）， week 2（baseline），week 4（post-intervention），week 8、12、16、20、24、28、32（follow-up）	The Beck Anxiety Inventory (BAI) is a self-rating scale used to assess a patient's anxiety symptoms. The scale consists of 21 items, each evaluating the degree of distress caused by anxiety symptoms. It uses a four-point scale from 1 to 4, with 1 indicating no symptoms and 4 indicating severe symptoms. The total score ranges from a minimum of 21 to a maximum of 84, with higher scores indicating more severe anxiety symptoms.
Beck Depression Inventory(BDI)	Week 0（recuitment）， week 2（baseline），week 4（post-intervention），week 8、12、16、20、24、28、32（follow-up）	The Beck Depression Inventory (BDI) is a self-rating scale used to assess a patient's depression symptoms. The BDI consists of 21 items that evaluate depression from the perspectives of symptoms, mood changes, and somatic symptoms. It uses a four-point scale with scores ranging from 0 to 3, where 0 indicates no symptoms and 3 indicates severe symptoms. The scores from each item are summed to give a total score, which ranges from a minimum of 0 to a maximum of 63. Higher scores indicate more severe depressive symptoms.
Fecal microbiota	week 2（baseline），week 8（post-intervention），week 12（follow-up）	Change in diversity and composition of the fecal microbiota as assessed by macrogenomic sequencing of feces.